Dna polymerase arrest by adducted trivalent chromium

Bridgewater, Laura C.; Manning, Francis C. R.; Woo, Elizabeth S.; Patierno, Steven R.

doi:10.1002/mc.2940090304

Cited by 113 publications

(91 citation statements)

References 59 publications

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“…Our observations are consistent with other spectroscopic studies that showed no major Cr(VI)-DNA interaction in vitro in the absence of reducing agents (5,8,30). However, in the presence of metabolizing system, where Cr(VI) is reduced to Cr(III), major Cr(III)-DNA complexation has been observed (5,8,10,11).…”

Section: Resultssupporting

confidence: 92%

“…When the concentration of Cr(III) increased further, DNA-DNA cross-links occurred to inhibit the polymerase activity. Trivalent chromium can bind purified DNA and form lesions capable of obstructing DNA replication in vitro (10,11). It has also been observed that intact Novikoff ascites hepatoma cells exposed to potassium chromate formed cross-linking of nuclear proteins to DNA (12).…”

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confidence: 99%

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A Comparative Study of Calf Thymus DNA Binding to Cr(III) and Cr(VI) Ions

Arakawa¹,

Ahmad

Naoui

et al. 2000

Journal of Biological Chemistry

257

118

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Chromium(VI) salts are well known to be mutagens and carcinogens and to easily cross the cell membranes. Because they are powerful oxidizing agents, Cr(VI) reacts with intracellular materials to reduce to trivalent form, which binds DNA. This study was designed to investigate the interaction of calf thymus DNA with Cr(VI) and Cr(III) in aqueous solution at pH 6.5-7.5, using Cr(VI)/DNA(P) molar ratios (r) of 1:20 to 2:1 and Cr(III)/ DNA(P) molar ratios (r) of 1:80 to 1:2. UV-visible and Fourier transform infrared (FTIR) difference spectroscopic methods were used to determine the metal ionbinding sites, binding constants, and the effect of cation complexation on DNA secondary structure. Spectroscopic results showed no interaction of Cr(VI) with DNA at low anion concentrations (r ‫؍‬ 1:20 to 1:1), whereas some perturbations of DNA bases and backbone phosphate were observed at very high Cr ( Chromium(VI) salts are well known to be mutagens and carcinogens and to easily invade the insides of cells (1). Cr(VI) produced DNA cross-links in rat tissues in vivo (2) and in cultured cells in vitro (3, 4). Although Cr(VI) damaged nuclear DNA in whole cells, no reaction of Cr(VI) with isolated DNA occurred in vitro at physiological pH in the absence of a metabolizing system (5). The Cr(VI) that is taken up is considered to be reduced by glutathione, cysteine, or ascorbic acid into Cr(III) (6), and the resulting cation reacts with DNA to form Cr(III)-DNA adducts. Because Cr(III) is a final form of chromium within the cell, the interaction of Cr(III) with DNA may play crucial role in the carcinogenetic action of Cr(VI) salts.The conversion of B form into Z form in the purine-pyrimidine sequence of DNA has been considered to be a factor in the transcriptional activity of genes (7). Cr(III) is found to interact with the poly(dG-dC) at low concentration and change B form to Z form in the presence of ethanol (8). However, Cr(III) at high concentration causes DNA condensation, inhibiting the alteration of B to Z structure (8). Moreover, the study on the effect of Cr(III) on DNA replication with single-stranded DNA template and micromolar concentration of Cr(III) revealed that Cr(III) bound in a dose-dependent manner to the template DNA and prevents DNA replication (9). However, if the unbound chromium was removed from the system by gel filtration, the rate of DNA replication by polymerase I (Klenow fragment) on the chromium-bound template increased more than 6-fold relative to control. This increase was paralleled by as much as a 4-fold increase in processivity and a 2-fold decrease in replication fidelity. When the concentration of Cr(III) increased further, DNA-DNA cross-links occurred to inhibit the polymerase activity. Trivalent chromium can bind purified DNA and form lesions capable of obstructing DNA replication in vitro (10, 11). It has also been observed that intact Novikoff ascites hepatoma cells exposed to potassium chromate formed cross-linking of nuclear proteins to DNA (12). Recently, Cr(III) was shown to cause mutation...

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Section: Resultssupporting

confidence: 92%

mentioning

confidence: 99%

A Comparative Study of Calf Thymus DNA Binding to Cr(III) and Cr(VI) Ions

Arakawa¹,

Ahmad

Naoui

et al. 2000

Journal of Biological Chemistry

257

118

View full text Add to dashboard Cite

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“…Treatment of pSV2neoTS with CrCl3 resulted in the dose-dependent formation of truncated molecules (Figure 7). After treatment with relatively low concentrations of CrCl3 (35, (36). A similar inhibition of polymerase action via the formation of chromium (III)-induced DNA-DNA cross-links has previously been reported by Snow and Xu (45).…”

Section: Discussionsupporting

confidence: 70%

Induction of internucleosomal DNA fragmentation by carcinogenic chromate: relationship to DNA damage, genotoxicity, and inhibition of macromolecular synthesis.

Manning

Blankenship

Wise

et al. 1994

Environ Health Perspect

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Hexavalent chromium (Cr) compounds are respiratory carcinogens in humans and animals. Treatment of Chinese hamster ovary cells with 150 and 300 pM sodium chromate (Na2CrO4) for 2 hr decreased colony-forming efficiency by 46 and 92%, respectively. These treatments induced dosedependent internucleosomal fragmentation of cellular DNA beyond 24 hr after chromate treatment. This fragmentation pattern is characteristic of apoptosis as a mechanism of cell death. These treatments also induced an immediate inhibition of macromolecular synthesis and delayed progression of cells through S-phase of the cell cycle. Cell growth (as evidenced by DNA synthesis) was inhibited for at least 4 days and transcription remained suppressed for at least 32 hr. Many of the cells that did progress to metaphase exhibited chromosome damage. Chromate caused the dose-dependent formation of DNA single-strand breaks and DNA-protein cross-links, but these were repaired 8 and 24 hr after removal of the treatment, respectively. In contrast, Cr-DNA adducts (up to 1/100 base-pairs) were extremely resistant to repair and were still detectable even 5 days after treatment. Compared with other regions of the genome, DNA-protein cross-links and Cr adducts were preferentially associated with the nuclear matrix DNA of treated cells, which was 4.5-fold enriched in actively transcribed genes. Chromium adducts, formed on DNA in vitro at a similar level to that detected in nuclear matrix DNA, arrested the progression of a DNA polymerase in a sequence-specific manner, possibly through the formation of DNA-DNA cross-links. Total RNA and mRNA synthesis and induction of expression of the inducible GRP78 gene were suppressed in a concentration-and time-dependent manner by chromate. The effects of chromate on GRP78 induction correlated most closely with the presence of DNA-protein cross-links but suppression of total RNA and mRNA synthesis correlated with the presence of DNA-Cr adducts in cells. These results suggest that the persistent Cr-DNA adducts may be responsible for the protracted cell cycle delay and transcriptional inhibition caused by chromate. Escape from apoptosis may be one of the steps involved in chromate-induced carcinogenesis. -Environ Health Perspect 102(Suppl 3): 159-167 (1994).

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“…Because no chromium deficiency has been consistently reported amongst healthy human populations (Stallings and Vincent 2006;Stearns 2007), the fact of its ''essentiality'' remains a controversial matter (Stearns 2000;Levina et al 2003;Stallings and Vincent 2006). Furthermore, because chromium may accumulate and is possibly genotoxic to animals and humans (Smith 1970;Debetto and Luciani 1988;Snow 1991;Bridgewater et al 1994;Stearns et al 1995;Błasiak and Kowalik 2000), excessive chromium intake (or exposure) should be avoided. For the two categories of adults in our study, the median and 95th percentile values are, respectively, 0.6 and 1.9 % (consumers of WB meat only) and 1.1 and 3.5 % (consumers of WB meat plus liver) of the safe limit established by the WHO (1996).…”

Section: Cadmium Lead and Chromium Exposure Assessments For Huntersmentioning

confidence: 99%

Cadmium, Lead, and Chromium in Large Game: A Local-Scale Exposure Assessment for Hunters Consuming Meat and Liver of Wild Boar

Danieli

Serrani

Primi

et al. 2012

Arch Environ Contam Toxicol

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Heavy metals are ubiquitous in soil, water, and air. Their entrance into the food chain is an important environmental issue that entails risks to humans. Several reports indicate that game meat can be an important source of heavy metals, particularly because of the increasing consumption of game meat, mainly by hunters. We performed an exposure assessment of hunters and members of their households, both adults and children, who consumed wild boar (WB) meat and offal. We estimated the amount of cadmium, lead, and chromium in the tissues of WB hunted in six areas within Viterbo Province (Italy) and gathered data on WB meat and offal consumption by conducting specific diet surveys in the same areas. The exposure to cadmium, lead, and chromium was simulated with specifically developed Monte Carlo simulation models. Cadmium and lead levels in WB liver and meat harvested in Viterbo Province (Italy) were similar to or lower than the values reported in other studies. However, some samples contained these metals at levels greater then the EU limits set for domestic animals. The chromium content of meat or liver cannot be evaluated against any regulatory limit, but our results suggest that the amounts of this metal found in WB products may reflect a moderate environmental load. Our survey of the hunter population confirmed that their consumption of WB meat and liver was greater than that of the general Italian population. This level of consumption was comparable with other European studies. Consumption of WB products contributes significantly to cadmium and lead exposure of both adults and children. More specifically, consumption of the WB liver contributed significantly to total cadmium and lead exposure of members of the households of WB hunters. As a general rule, liver consumption should be kept to a minimum, especially for children living in these hunter households. The exposure to chromium estimated for this population of hunters may be considered to be safe. However, a specific and complete assessment of chromium speciation in relevant dietary and environmental situations should be conducted.

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Dna polymerase arrest by adducted trivalent chromium

Cited by 113 publications

References 59 publications

A Comparative Study of Calf Thymus DNA Binding to Cr(III) and Cr(VI) Ions

A Comparative Study of Calf Thymus DNA Binding to Cr(III) and Cr(VI) Ions

Induction of internucleosomal DNA fragmentation by carcinogenic chromate: relationship to DNA damage, genotoxicity, and inhibition of macromolecular synthesis.

Cadmium, Lead, and Chromium in Large Game: A Local-Scale Exposure Assessment for Hunters Consuming Meat and Liver of Wild Boar

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